Interactions between marine benthic macroinvertebrates and their sedimentary environment

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Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

BACKGROUND: It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. METHODS: We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3) and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. RESULTS: Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium), although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating endothelial cells, and the cross sectional area of vessel profiles were significantly increased in response to VEGF-D in comparison to control tumor cells. In contrast, no significant changes were noted in myometrial blood vessels. In addition, examples of invading cells or tumor emboli were observed in mice receiving VEGF-D expressing 293EBNA cells. CONCLUSIONS: These results illustrate that VEGF-D over-expression has differential effects on the uterine vasculature. These effects may facilitate VEGF-D's ability to promote endometrial cancer metastasis and disease progression

The revitalised Fonofale as a research paradigm: A perspective on Pacific sexuality and reproduction research

Research into Pacific peoples’ sexuality and reproduction is often complex and conflicts with social tapu. Historically, Pacific sexuality and reproduction research had been approached using a deficits-based lens with minimal congruence of Pacific cultural values. We offer a revitalised Fonofale model (Pulotu-Endemann, 1995) as a research paradigm that centres tapu in all considerations and decisions surrounding the research. This revitalised model offers a strengths-based approach that can promote valuable collection of, and meaningful engagement with data. We offer a case study which utilised this research paradigm as an overarching strategy. Te Tīpani Project was a mixed methods investigation into eighty-two Pacific tertiary students’ understandings of sexuality and reproduction. Pacific research methods and methodologies, including the Kakala model and Talanoa method supported the integration of the paradigm into components of the study. We encourage researchers to utilise this strategy to fulfil their research obligations, as facilitators and guardians (mana tiaki) of the research environment. Pacific research methods, methodologies and epistemologies hold an important place in the field of sensitive Pacific well-being research by enabling cultural consideration and responsiveness

The Royal Zoological Society of Scotland’s Approach to Assessing and Promoting Animal Welfare in Collaboration with Universities

Good zoos have four aims—to conserve species, educate the public, engage in research, and provide recreation—all of which can only be achieved when underpinned by high animal welfare standards. In this paper, we share the approach that The Royal Zoological Society of Scotland’s (RZSS) Edinburgh Zoo and Highland Wildlife Park take to animal welfare. We highlight the role that animal welfare research, in collaboration with universities, has had in enabling the zoo to take an evidence-based approach to welfare and to put findings into practice. We share the collaborative process through which we developed and piloted the current animal welfare assessment tools, how they were validated, and how they were tested for reliability as part of a long-term collaboration between the Royal Zoological Society of Scotland and the University of Stirling: (1) the RZSS Welfare Assessment Tool, a 50-question animal welfare assessment adapted from the British and Irish Association of Zoos and Aquariums (BIAZA) Toolkit; and (2) the Stirling Toolkit, a package of evidence-based resources for behavioural-data collection. Our aim is to facilitate standardised, evidence-based approaches to assessing animal welfare which, when finalised, can be used collaboratively across zoos

Early death during chemotherapy in patients with small-cell lung cancer: derivation of a prognostic index for toxic death and progression

Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were stored in a database and logistic regression analyses were performed to identify predictive factors for early death. During the first cycle, 118 out of 937 patients (12.6%) died. In 38 patients (4%), the cause of death was sepsis. Significant risk factors were age, performance status (PS), lactate dehydrogenase (LDH) and treatment with epipodophyllotoxins and platinum in the first cycle (EP). Risk factors for ENTD were age, PS and LDH. Extensive stage had a hazard ratio of 1.9 (P = 0.07). Risk factors for ETD were EP, PS and LDH, whereas age and stage were not. For EP, the hazard ratio was as high as 6.7 (P = 0.0001). We introduced a simple prognostic algorithm including performance status, LDH and age. Using a prognostic algorithm to exclude poor-risk patients from trials, we could minimize early death, improve long-term survival and increase the survival differences between different regimens. We suggest that other groups evaluate our algorithm and exclude poor prognosis patients from trials of dose intensification. © 1999 Cancer Research Campaig

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

Weed suppression and tolerance in winter oats

A crops ability to both suppress weed growth and tolerate weed competition is a key consideration when taking an agroecological approach to weed management. Amongst other cereals, oats are widely considered to have superior weed competitiveness yet studies examining competitive ability between oat varieties are rare. We investigated the ability of oats to suppress weeds and yield in the presence of competition from weeds in trials involving five husked and three naked oat varieties at an organic site in the east of England over four trial years (2009-13). We identified a number of key traits that were important for weed suppression including establishment rates, tillering ability, and early Leaf Area Index (LAI) which highlight the importance of rapid early growth rates. Furthermore, taller varieties tended to be more weed tolerant but not necessarily more suppressive. Trade-offs between competitive traits and yield were not found in this study. Crop tillering ability was highlighted as an important trait for selection due to its beneficial effects on weed suppression as well as grain yield and also its high heritability

Effects of hot isostatic pressing on the elastic modulus and tensile properties of 316L parts made by powder bed laser fusion

The microstructure and mechanical properties of 316 L steel have been examined for parts built by a powder bed laser fusion process, which uses a laser to melt and build parts additively on a layer by layer basis.Relative density and porosity determined using various experimental techniques were correlated against laser energy density. Based on porosity sizes, morphology and distributions, the porosity was seen to transition between an irregular, highly directional porosity at the low laser energy density and a smaller, more rounded and randomly distributed porosity at higher laser energy density, thought to be caused by keyhole melting. In both cases, the porosity was reduced by hot isostatic pressing (HIP).High throughput ultrasound based measurements were used to calculate elasticity properties and show that the lower porosities from builds with higher energy densities have higher elasticity moduli in accordance with empirical relationships, and hot isostatic pressing improves the elasticity properties to levels associated with wrought/rolled 316 L. However, even with hot isostatic pressing the best properties were obtained from samples with the lowest porosity in the as-built condition.A finite element stress analysis based on the porosity microstructures was undertaken, to understand the effect of pore size distributions and morphology on the Young's modulus. Over 1–5% porosity range angular porosity was found to reduce the Young's modulus by 5% more than rounded porosity. Experimentally measured Young's moduli for samples treated by HIP were closer to the rounded trends than the as-built samples, which were closer to angular trends.Tensile tests on specimens produced at optimised machine parameters displayed a high degree of anisotropy in the build direction and test variability for as-built parts, especially between vertical and horizontal build directions. The as-built properties were generally found to have a higher yield stress, but lower upper tensile strength and elongation than published data for wrought/hot-rolled plate 316 L. The hot isostatically pressed parts showed a homogenisation of the properties across build directions and properties much more akin to those of wrought/hot-rolled 316 L, with an increase in elongation and upper tensile strength, and a reduction in yield over the as-built samples

Improving the normalization of complex interventions: measure development based on normalization process theory (NoMAD): study protocol

<b>Background</b> Understanding implementation processes is key to ensuring that complex interventions in healthcare are taken up in practice and thus maximize intended benefits for service provision and (ultimately) care to patients. Normalization Process Theory (NPT) provides a framework for understanding how a new intervention becomes part of normal practice. This study aims to develop and validate simple generic tools derived from NPT, to be used to improve the implementation of complex healthcare interventions.<p></p> <b>Objectives</b> The objectives of this study are to: develop a set of NPT-based measures and formatively evaluate their use for identifying implementation problems and monitoring progress; conduct preliminary evaluation of these measures across a range of interventions and contexts, and identify factors that affect this process; explore the utility of these measures for predicting outcomes; and develop an online users’ manual for the measures.<p></p> <b>Methods</b> A combination of qualitative (workshops, item development, user feedback, cognitive interviews) and quantitative (survey) methods will be used to develop NPT measures, and test the utility of the measures in six healthcare intervention settings.<p></p> <b>Discussion</b> The measures developed in the study will be available for use by those involved in planning, implementing, and evaluating complex interventions in healthcare and have the potential to enhance the chances of their implementation, leading to sustained changes in working practices